In 1803, Trimble was elected to represent Bourbon County in the Kentucky House of Representatives.[1] During his single term in the legislature, he found that he disliked the life of a politician, and thereafter refused election to any public office, including two nominations to the U.S. Senate.[1]

On April 11, 1826, President John Quincy Adams nominated Trimble to a seat on the Supreme Court of the United States vacated by the death of Justice Thomas Todd.[2] Trimble was Adams' only appointment to the Supreme Court and the first U.S. District Judge to be appointed to the Supreme Court.[2] Adams is said to have appointed Trimble because of the "Kentucky" vacancy created by the death of Thomas Todd and on the advice of Henry Clay, who was Secretary of State.[citation needed] Trimble was again confirmed by the United States Senate on May 9, 1826, and received his commission the same day.[4]

As a member of the court, Trimble generally agreed with the opinions of Chief Justice John Marshall.[2] In a notable departure, he wrote the majority opinion in the case of Ogden v. Saunders; Marshall wrote the dissenting opinion in the case.[2] Trimble served on the Court until his sudden death from a "malignant bilious fever" on August 25, 1828.[2] He died in Paris, Kentucky and was buried in the Paris Cemetery. Trimble County, Kentucky is named in his honor.[5]